Genetic studies of cyc1 and cyc7 mutants of yeast, along with protein analysis of their gene products, iso-1 and iso-2-cytochromes c, respectively, has led to the identification of the nucleotide sequences of various mutants including UAA and UAG nonsense mutants, missense mutants, frameshift mutants and mutants of the AUG initiation codon. In most instances the nucleotide sequences of the mutational lesions were deduced from amino acid changes in altered but function iso-cytochromes c from intragenic revertants or suppressed strains. The isolation of appropriate mutants have been facilitated by enrichment techniques for both forward and reverse mutations which are based, respectively, on defectiveness and functioning of cytochrome c for lactate utilization. This iso-cytochromes c system is being employed in numerous investigations at the molecular level including: (a) identification of amino acid residues inserted by various nonsense suppressors and the determination of efficiencies of suppression; (b) determination of the specific action of numerous mutagens; (c) investigation of the nucleotide sequences that control the initiation of translation and the question of polycistronic mRNA in eukaryotes; (d) determination of the relationship of recombination frequencies and nucleotide alterations; (e) determination of which specific amino acid residues are required or can be varied in functioning iso-1-cytochrome c; (f) determination of the mutant loci that control the levels of iso-1 and iso-2-cytochrome c and (g) determination of the levels of iso-1-cytochrome c and the levels of its mRNA in normal and mutant strains of yeast under different physiological conditions. BIBLIOGRAPHIC REFERENCES: Liebman, S.W. and F. Sherman, Inhibition of growth by amber suppressors in yeast. Genetics 82, 233-249 (1976). Moore, C.W. and F. Sherman, Role of DNA sequences in genetic recombination in the iso-1-cytochrome c. gene of yeast. II. Comparison of mutants altered at the same and nearby sites. Genetics (in press, January 1977).